In vivo microCT-arthrography is a valuable tool for detection of minor cartilage alterations and distinguishes different stages of cartilage degeneration in a small animal model. Since microCT, at the same time, also visualizes osteophyte formation and changes in the underlying subchondral bone structures, the technique will be very useful for longitudinal overall assessment of the development of (osteo)arthritis and to study interventions in small animal models.

Objective. Evaluation of macrophage activation may provide essential information about the etiology and progression rate of osteoarthritis (OA). Activated macrophages abundantly express folate receptor ␤ (FR␤), which can be targeted using radioactive-labeled folic acid. This study was undertaken to investigate whether macrophage activation can be monitored in small animal models of OA using a folate radiotracer and to determine whether macrophage activation differs in different models of OA with different OA progression.Methods. Two rat models of OA were used: the mono-iodoacetate (MIA) model, which is a fastprogressing biochemically induced model, and the anterior cruciate ligament transection (ACLT) model, which induces OA at a slower pace. Images were obtained using high-resolution small animal singlephoton-emissioncomputedtomography/computedtomography. The specificity of the technique was tested by eradicating macrophages using clodronate-laden liposomes and blockade of FR␤ by cold folic acid.Results. The MIA model had high initial macrophage activation, with a peak after 2 weeks which disappeared after 8 weeks. The ACLT model showed less activation but was still active 12 weeks after induction. The technique allowed monitoring of the disease process over time, in which late stages of the disease showed less macrophage activation than early stages, especially in the fast-progressing MIA model of OA.Conclusion. Our findings indicate that macrophage activation in experimental OA can clearly be demonstrated and monitored by the folate radiotracer. The high resolution, high sensitivity, and high specificity of the technique allow clear localization of macrophage activity in a disease model that is not known for abundant macrophage involvement.

Contrast diffusion into articular cartilage detected with CTa correlates with sGAG content and to a lesser extent with structural composition of cartilage ECM. CTa may be clinically applicable to quantitatively measure the quality of articular cartilage.

In vivo microCT arthrography (mCTa) can be used to measure both quantity (volumetric) and quality (glycosaminoglycan content) of cartilage. This study investigated the accuracy of four segmentation techniques to isolate cartilage from mCTa datasets and then used the most accurate one to investigate if the mCTa method could show osteoarthritic changes in rat models during longitudinal follow-up. Volumetric measurements and glycosaminoglycan contents of patellar cartilage from in vivo mCTa-scans were compared with an ex vivo gold standard mCT-scan. Cartilage was segmented with three global thresholds and one local threshold algorithm. Comparisons were made for healthy and osteoarthritic cartilage. Next, three rat models were investigated for 24 weeks using mCTa. Osteoarthritis was induced by injection with a chemical (mono-iodoacetate), a surgical intervention (grooves applied in articular cartilage), and via exercise (strenuous running). After euthanasia, all knee joints were isolated for histology. Local thresholds accurately segmented cartilage from in vivo mCTa scans and best measured cartilage quantity and glycosaminoglycan content. Each of the three osteoarthritic rat models showed a specific pattern of osteoarthritis progression. All mCTa results were comparable to histology. In vivo mCTa is a sensitive technique for imaging cartilage degradation. Local thresholds enhanced the sensitivity of this method and will probably more accurately detect disease-modulating effects from interventional strategies. The data from rat models may serve as a reference for the time sequence of cartilage degeneration during in vivo testing of new strategies in osteoarthritis treatment. Keywords: micro computed tomography arthrography; small animal models; mono-iodoacetate; groove; strenuous running Current treatment strategies for osteoarthritis (OA) are limited, and end-stage OA is treated with costly, invasive joint replacement surgery. Disease-modifying osteoarthritic drugs (DMOADs) that may target early disease progression are unavailable for clinical use. Therefore, a large need exists for testing the potential of DMOADs in animal OA models. OA research in small animals using in vivo mCT has mainly been limited to subchondral bone changes, 1 since mCT is not suited for soft tissue imaging. However, mCT-arthrography (mCTa) can accurately measure changes within cartilage. Similar to delayed gadolinium enhanced magnetic resonance imaging (dGEMRIC), 2,3 cartilage can be imaged and its sulphated glycosaminoglycan (sGAG) content determined using a suitable X-ray contrast agent. 4,5 As sGAG forms the main component of the negative fixed charge density (FCD) in cartilage, the influx of a negatively charged agent is inversely related to sGAG content. With OA progression, the FCD diminishes due to sGAG depletion and consequently more contrast agent will penetrate, which can be measured as a surrogate for cartilage quality.Previous publications described an in vitro technique where cartilage samples were saturated in ioxag...

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